This project will continue to delineate and quantitate in dogs the role of the hepatic extraction of insulin and glucagon in maintaining homeostasis of these two hormones under different physiological conditions. Previous studies have indicated that approximately 50% of the insulin presented to the liver is removed in a single transhepatic passage. Administration of glucose into the duodenum caused markedly increased pancreatic secretion of insulin which was associated with increased hepatic extraction of insulin. The increased hepatic extraction of insulin appeared to reflect the greater amounts of insulin reaching the liver rather than the effects of glucose since a similar increase in hepatic extraction was observed when increasing amounts of insulin were infused into the portal vein. In these experiments there was a decrease in blood glucose. Such studies utilizing anesthetized dogs with catheters in the femoral artery, portal vein and inferior vena cava and electromagnetic flow probes on the portal vein, hepatic artery and inferior vena cava will be extended to measure hepatic extraction of glucagon during fasting and following arginine and pancreozymin infusions, all of which should increase pancreatic glucagon production. Additional studies will be done to assess hepatic extraction of insulin after i.v. glucose, tolbutamide, arginine and glucagon infusions. Effects of various hormones on hepatic extraction of insulin and glucose will be evaluated.